Monoclonal gammopathy of renal significance from the perspective of nephrologists

Kootae Park; Soon Hyo Kwon

doi:10.1007/s44313-024-00027-5

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Blood Res (2024) 59:28

Published online August 12, 2024

https://doi.org/10.1007/s44313-024-00027-5

Monoclonal gammopathy of renal significance from the perspective of nephrologists

Kootae Park¹ and Soon Hyo Kwon^1*

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¹ Division of Nephrology, Hyonam Kidney Laboratory, Soonchunhyang University Hospital, ⁵⁹ Daesagwan‑Ro, Yongsan‑Gu, Seoul, South Korea

Correspondence to : *Correspondence:
Soon Hyo Kwon
ksoonhyo@schmc.ac.kr

Received: June 17, 2024; Accepted: July 4, 2024

© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Abstract

Kidney disease is a frequent complication of multiple myeloma and other malignancies associated with monoclonal gammopathies. Additionally, dysproteinemia-related kidney disease can occur independently of overt multiple myeloma or hematologic malignancies. Monoclonal gammopathy of renal significance (MGRS) is a spectrum of disorders in which a monoclonal immunoglobulin produced by a benign or premalignant B-cell or plasma cell clone causes kidney damage. MGRS-associated renal disease manifests in various forms, including immunoglobulin-associated amyloidosis, monoclonal immunoglobulin deposition diseases (light chain, heavy chain, and combined light and heavy chain deposition diseases), proliferative glomerulonephritis with monoclonal immunoglobulin deposits, C3 glomerulopathy with monoclonal gammopathy, and light chain proximal tubulopathy. Although MGRS is a nonmalignant or premalignant hematologic condition, it has significant renal implications that often lead to progressive kidney damage and, eventually, end-stage kidney disease. This review discusses the epidemiology, pathogenesis, and management of MGRS and focuses on the perspective of nephrologists.

Keywords Chronic kidney disease, Kidney biopsy, Light chain, Monoclonal gammopathy

Article

REVIEW

Blood Res 2024; 59():

Published online August 12, 2024 https://doi.org/10.1007/s44313-024-00027-5

Monoclonal gammopathy of renal significance from the perspective of nephrologists

Kootae Park¹ and Soon Hyo Kwon^1*

¹ Division of Nephrology, Hyonam Kidney Laboratory, Soonchunhyang University Hospital, ⁵⁹ Daesagwan‑Ro, Yongsan‑Gu, Seoul, South Korea

Correspondence to:*Correspondence:
Soon Hyo Kwon
ksoonhyo@schmc.ac.kr

Received: June 17, 2024; Accepted: July 4, 2024

Abstract

Keywords: Chronic kidney disease, Kidney biopsy, Light chain, Monoclonal gammopathy

Abstract

Table 1 . Renal lesions associated with monoclonal gammopathy of renal significance.

Lesion (proportion of lesions, %)	Renal symptoms	Light microscopy findings	IF findings	Ultrastructural findings (deposition)
Immunoglobulin-related amyloidosis (80%)	Proteinuria, hematuria, hypertension, CKD	Congo red-positive mesangial and capillary wall deposits (dichroism + birefringence under polarized light) Vascular and tubulo-interstitial involvement (common)	AL: LC deposits, mostly λ AH: HC deposits (g1 or g4 or a) with first constant domain (CH1) deletion AHL: LC and HC deposits, mostly γ + λ or α + κ	Randomly arranged unbranched fibrils 7–14 nm in diameter (organized deposits)
MIDD (78%–100%)	Proteinuria, microscopic hematuria, hypertension, CKD	Nodular glomerulosclerosis (constant in HCDD) Thickened TBM and vascular walls	Linear deposits along the TBM and GBM and around arteriolar/arterial myocytes LCDDL: mostly κ (Vk4) HCDD: truncated HC (g1, g3, g4, or a) with CH1 deletion C3 deposits in g1 and g3 HCDD LHCDD: LC truncated HC deposits	Amorphous deposits in the TBM, GBM, mesangium, and arteriolar/arterial walls (nonorganized deposits)
PGNMID (96%)	Proteinuria, microscopic hematuria	Membranous proliferative GN, endocapillary proliferative GN, mesangial GN	Granular deposits in the mesangium and capillary wall Monotypic IgG deposits IgG3 (most common), IgG1, or IgG2 (k41) Rarely, monotypic IgM, IgA, or LC deposits C3 C1q deposits	Nonorganized granular deposits in the mesangium, subendothelial, and/or subepithelial zone (nonorganized deposit)
C3 glomerulopathy with monoclonal gammopathy (40%–90%)	Proteinuria, microscopic hematuria, hypertension, CKD	Membranous proliferative GN, endocapillary proliferative GN	Granular C3 deposits in the mesangium and capillary wall No or few Ig deposits	Sausage-shaped intramembranous and large, rounded mesangial electrondense deposits III-defined, mesangial, intramembranous, and subendothelial electrondense deposits in C3GN humps common in DDD and C3GN (nonorganized C3 deposit)
Monoclonal fibrillary GN (55%–98%)		Mesangial proliferative GN, mesangial expansion, amorphous eosinophil material in the capillary wall	Global mesangial and glomerular capillary wall, ill-defined deposits (IgG, C3, κ, and λ)	Randomly arranged 12-nm to 24-nm fibrils in the GBM and mesangial matrix (organized deposit)
Type I cryoglobulinemic GN (47%–52%) and type II cryoglobulinemic GN (20%)	Proteinuria, microscopic hematuria, hypertension, AKI, anuria, CKD	Membranous proliferative GN, endocapillary GN, glomerular thrombi (common)	Granular deposits in the mesangium, capillary wall (predominantly subendothelial), vascular walls, and glomerular thrombi Monotypic IgG, IgM, or IgA (κ > λ) C3, C4, and C1q deposits	Microtubules (10–90 nm), extracellular and intracellular crystals (organized deposit)
Immunotactoid GN (25%–50%)	Proteinuria, microscopic hematuria, hypertension	Mesangial GN with membranous features, membranous proliferative GN	Granular/smudgy deposits in the mesangium and capillary wall (predominantly subepithelial) Monotypic IgG deposits (IgG14, IgG24, IgG3) (k41) C3, C4, and C1q deposits	Parallel-arranged microtubules (10–60 nm) with a hollow core (organized deposit)
Cryocrystalglobulin or crystal globulin nephropathy (18%)	Proteinuria, pyuria, CKD	Crystals in all capillary lumens, glomerular epithelium, and convoluted tubules	Large crystals in the vessels and glomeruli with IgG and κ	Large intraglomerular capillary electron-dense crystal (organized deposit)
Crystal-storing histiocytosis (8%)	Fanconi syndrome	Histiocytes with crystalline inclusions in the interstitium and perirenal fat PTC atrophy and dedifferentiation	PTC LC inclusions, mostly κ	Crystals (needle-shaped) within histiocytes and occasionally in the PTC and glomerular cells (organized deposit)

AH Immunoglobulin heavy chain amyloidosis, AHL Immunoglobulin heavy chain and light chain amyloidosis, AL Immunoglobulin light chain amyloidosis, CKD Chronic kidney disease, DDD Dense deposit disease, IF Immunofluorescence, Ig Immunoglobulin, GBM Glomerular basement membrane, GN Glomerulonephritis, HC Heavy chain, HCDD Heavy chain deposition disease, LC Light chain, LHCDD Light chain deposition disease, MIDD Monoclonal immunoglobulin deposition disease, PGNMID Proliferative glomerulonephritis with monoclonal gammopathy, PTC Peritubular capillary, TBM Tubular basement membrane.